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Blast-Mediated Traumatic Brain Injury Exacerbates Retinal Damage and Amyloidosis in the APPswePSENd19e Mouse Model of Alzheimer's Disease
Journal article   Open access   Peer reviewed

Blast-Mediated Traumatic Brain Injury Exacerbates Retinal Damage and Amyloidosis in the APPswePSENd19e Mouse Model of Alzheimer's Disease

Matthew M Harper, Adam Hedberg-Buenz, Judith Herlein, Eric E Abrahamson, Michael G Anderson, Markus H Kuehn, Randy H Kardon, Pieter Poolman and Milos D Ikonomovic
Investigative ophthalmology & visual science, Vol.60(7), pp.2716-2725
06/03/2019
DOI: 10.1167/iovs.18-26353
PMCID: PMC6735799
PMID: 31247112
url
https://doi.org/10.1167/iovs.18-26353View
Published (Version of record) Open Access

Abstract

Traumatic brain injury (TBI) is a risk factor for developing chronic neurodegenerative conditions including Alzheimer's disease (AD). The purpose of this study was to examine chronic effects of blast TBI on retinal ganglion cells (RGC), optic nerve, and brain amyloid load in a mouse model of AD amyloidosis. Transgenic (TG) double-mutant APPswePSENd19e (APP/PS1) mice and nontransgenic (Non-TG) littermates were exposed to a single blast TBI (20 psi) at age 2 to 3 months. RGC cell structure and function was evaluated 2 months later (average age at endpoint = 4.5 months) using pattern electroretinogram (PERG), optical coherence tomography (OCT), and the chromatic pupil light reflex (cPLR), followed by histologic analysis of retina, optic nerve, and brain amyloid pathology. APP/PS1 mice exposed to blast TBI (TG-Blast) had significantly lower PERG and cPLR responses 2 months after injury compared to preblast values and compared to sham groups of APP/PS1 (TG-Sham) and nontransgenic (Non-TG-Sham) mice as well as nontransgenic blast-exposed mice (Non-TG-Blast). The TG-Blast group also had significantly thinner RGC complex and more optic nerve damage compared to all groups. No amyloid-β (Aβ) deposits were detected in retinas of APP/PS1 mice; however, increased amyloid precursor protein (APP)/Aβ-immunoreactivity was seen in TG-Blast compared to TG-Sham mice, particularly near blood vessels. TG-Blast and TG-Sham groups exhibited high variability in pathology severity, with a strong, but not statistically significant, trend for greater cerebral cortical Aβ plaque load in the TG-Blast compared to TG-Sham group. When combined with a genetic susceptibility for developing amyloidosis of AD, blast TBI exposure leads to earlier RGC and optic nerve damage associated with modest but detectable increase in cerebral cortical Aβ pathology. These findings suggest that genetic risk factors for AD may increase the sensitivity of the retina to blast-mediated damage.
 Optic Nerve - pathology Brain Injuries, Traumatic - complications Male Retinal Diseases - metabolism Retinal Ganglion Cells - metabolism Alzheimer Disease - pathology Retinal Ganglion Cells - pathology Brain - metabolism Reflex, Pupillary - physiology Blast Injuries - complications Retinal Diseases - etiology Amyloid beta-Peptides - metabolism Amyloid beta-Protein Precursor - metabolism Female Disease Models, Animal Electroretinography Amyloidosis - pathology Tomography, Optical Coherence Blast Injuries - metabolism Mice, Transgenic Blast Injuries - pathology Animals Brain Injuries, Traumatic - metabolism Brain Injuries, Traumatic - pathology Brain - pathology Mice Retinal Diseases - physiopathology Amyloidosis - metabolism Optic Nerve - metabolism

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